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Updated: Jun 13, 2025
Lipidomics and Transcriptomics in Neurological Diseases
Published on: March 18, 2022
Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic
Wei Wei1,2, Seyed Siyawasch Justus Lattau1, Wenqiang Xin1
1Department of Neurology, University Medicine Göttingen (UMG), University of Göttingen, 37075, Göttingen, Germany.
Abstract:
Microglia are critically involved in post-stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro-inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD-rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post-stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF-α, IL-6, and IL-1β as well as a pro-inflammatory phenotype and differentially expressed lipid metabolism-related genes. These post-ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post-ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury.
Insights
Lipid droplets (LDs) accumulate in microglia after stroke, promoting inflammation and worsening brain injury. Targeting these LD-rich microglia (LDRM) may offer new therapeutic strategies for stroke recovery.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key players in post-stroke inflammation.
- Lipid droplet (LD) accumulation in microglia is linked to dysfunction and inflammation in aging and neurodegenerative diseases.
- The role of LD-rich microglia (LDRM) in stroke remains unclear.
Purpose of the Study:
- To investigate microglial LD accumulation patterns and inflammatory signaling during stroke.
- To explore the temporal and spatial dynamics of lipid profiles and microglial phenotypes post-stroke.
- To elucidate the relationship between microglial lipid metabolism and inflammatory responses in ischemic brain injury.
Main Methods:
- Utilized in vitro and in vivo stroke models.
- Analyzed microglial LD accumulation and perilipin 2 (PLIN2) expression.
- Assessed inflammatory markers (TNF-α, IL-6, IL-1β) and gene expression related to lipid metabolism.
- Examined spatial and temporal lipid profile dynamics, including cholesteryl ester and triacylglycerol levels.
Main Results:
- Microglia showed increased LD accumulation and PLIN2 expression under hypoxia and stroke conditions.
- LDRM exhibited a pro-inflammatory phenotype with elevated TNF-α, IL-6, and IL-1β.
- Distinct spatial and temporal changes in lipid profiles, particularly cholesteryl esters and triacylglycerols, were observed.
- Differential expression of lipid metabolism-related genes was noted in LDRM.
Conclusions:
- Stroke induces significant LD accumulation and pro-inflammatory activation in microglia.
- Microglial lipid profiles dynamically change post-ischemia, exacerbating inflammation.
- A reciprocal relationship exists between microglial phenotype, lipid metabolism, and brain injury progression during stroke.
